Heterozygos eletion of β-catenin in early cardiogenesis attenuated the heart growth and affected on canonical Wnt kinetics

  • O. L. Palchevska Institute of Molecular Biology and Genetics of Natl. Acad. Sci. of Ukraine, Ukraine, 03680, Kyiv, Akad. Zabolotnogo str., 150
  • A. A. Hazaeeva Karazin Kharkiv National University, Ukraine, 61022, Kharkiv, Svobody Sqr., 4
  • V. V. Balatskyi Institute of Molecular Biology and Genetics of Natl. Acad. Sci. of Ukraine, Ukraine, 03680, Kyiv, Akad. Zabolotnogo str., 150
  • T. P. Ruban Institute of Molecular Biology and Genetics of Natl. Acad. Sci. of Ukraine, Ukraine, 03680, Kyiv, Akad. Zabolotnogo str., 150
  • L. L. Matsevych Institute of Molecular Biology and Genetics of Natl. Acad. Sci. of Ukraine, Ukraine, 03680, Kyiv, Akad. Zabolotnogo str., 150
  • O. O. Piven Institute of Molecular Biology and Genetics of Natl. Acad. Sci. of Ukraine, Ukraine, 03680, Kyiv, Akad. Zabolotnogo str., 150

Abstract

Aim. In our present work, we have analyzed newborn and embryonic heart under the β-catenin haploinsufficiency. Methods. Beta-catenin conditional knockout mice were bred with α-MHC-Cre transgenic mice. In such way we generate the β-catenin haploinsufficient new born (P1-2) and embryonic hearts (E12,5 an E14,5) With rtPCR using we analyze the canonical WNT signalling kinetics in embryonic and newborn hearts. Namely we have analyzed the level of TСF-4, Axin2, c-Fos and CyclinD2 genes expression. Beside of this we have studied the γ-catenin gene expression un-der normal and β-catenin haploinsufficient conditions. Results. Cardiac β-catenin knockout leads attenuated newborn heart growth and associated with γ-catenin expression up-regulation. Canonical Wnt signalling activated in later cardiogenesis (E12,5-14,5) in WT heart and downregulated in newborns. Conclusions. We have shown the importance of canonical Wnt during later cardiogenesis. Thus β-catenin haploinsufficiency leads to violation of WNT kinetic in latter embryos and attenuated the heart growth.
Keywords: heart development, cardiogenesis, WNT signalling, β-catenin, γ-catenin.

References

Bruneau B.G. Signaling and transcriptional networks in heart development and regeneration. Cold Spring Harb Perspect Biol. 2013. No. 5. Р. a008292. doi: 10.1101/cshperspect.a008292.

Freire A.G., Resende T.P., Pinto-do O.P. Building and repairing the heart: what can we learn from embryonic development? BioMed Res. Int. 2014. Р. 679168. doi: 10.1155/2014/679168.

Bergmann M.W. WNT signaling in adult cardiac hypertrophy and remodeling: lessons learned from cardiac development. Circ Res. 2010. No. 107. Р. 1198–1208. doi: 10.1161/CIRCRESAHA.110.223768.

Jain R., Li D., Gupta M., Manderfield L.J., Ifkovits J.L., Wang Q., Liu F., Liu Y., Poleshko A., Padmanabhan A., Raum J.C., Li L., Morrisey E.E., Lu M.M., Won K.J., Epstein J.A. HEART DEVELOPMENT. Integration of Bmp and Wnt signaling by Hopx specifies commitment of cardiomyoblasts. Science. 2015. No. 348. Р.aaa6071. doi: 10.1126/science.aaa607.

Piven O.O. Kostetskii I.E., Macewicz L.L., Kolomiets Y.M., Radice G.L., Lukash L.L. Requirement for N-cadherin-catenin complex in heart development. Exp Biol Med. 2011. No. 236. Р. 816–822. doi: 10.1258/ebm.2011.010362.

Palchevska O.L., Balatskii V.V., Andrejeva A.O., Macewicz L.L., Piven O.O., Lukash L.L. Embryonically induced β-catenin haploinsufficiency attenuates postnatal heart development and causes violation of foetal genes program. Biopolymers and Cell. 2013. V. 29, No. 2. P. 124–130. doi: 10.7124/bc.00080F

Pal'chevs'ka O.L., Khazieieva A.A., Machushynets' N.N., Ruban T.P., Matsevych L.L., Piven' O.O. Vplyv deletsii hena β-kateninu na morfolohiiu ta fiziolohiiu kardiomiotsytiv za umov dii stymuliatoriv hipertrofii. Faktory eksperymental'noi evoliutsii orhanizmiv. K.: Lohos, 2016. V. 18. P. 242–248. [in Ukrainian]

Agah R., Frenkel P.A., French B.A., Michael L.H., Overbeek P.A., Schneider M.D. Gene recombination in postmitotic cells. Targeted expression of Cre recombinase provokes cardiac-restricted, site-specific rearrangement in adult ventricular muscle in vivo. J. Clin. Invest. 1997. No. 100. Р. 169–179. doi: 10.1172/JCI119509

Nagy A., Gertsenstein M., Vintersten K., Behringer R. Manipulating the Mouse Embryo: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 2003.

Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006. V. 3, No. 127. Р. 469–480. doi: 10.1016/j.cell.2006.10.018

Stepniak E., Radice G.L., Vasioukhin V. Adhesive and signaling functions of cadherins and catenins in vertebrate development. Cold Spring Harb Perspect Biol. 2009. No. 1. Р. a002949. doi: 10.1101/cshperspect.a002949.

Butz S., Stappert J., Weissig H., Kemler R. Plakoglobin and beta-catenin: distinct but closely related. Science. 1992. No. 257. Р. 1142–1144. doi: 10.1126/science.257.5073.1142-a

Zhurinsky J., Shtutman M., Ben-Ze'ev A. Differential mechanisms of LEF/TCF family–dependent transcriptional activation by beta-catenin and plakoglobin. Mol Cell Biol. 2000. V. 20. P. 4238–4252. doi: 10.1128/MCB.20.12.4238-4252.2000

Mahendram S., Kelly K.F., Paez-Parent S., Mahmood S., Polena E., Cooney A.J., Doble B.W. Ectopic gamma-catenin expression partially mimics the effects of stabilized beta-catenin on embryonic stem cell differentiation. PloS one. 2013. V. 8. P. e65320. doi: 10.1371/journal.pone.0065320.

Aktary Z., Pasdar M. Plakoglobin represses SATB1 expression and decreases in vitro proliferation, migration and invasion. PloS one. 2013. V. 8. P. e78388. doi: 10.1371/journal.pone.0078388.

Swope D., Cheng L., Gao E., Li J., Radice G.L. Loss of cadherin-binding proteins beta-catenin and plakoglobin in the heart leads to gap junction remodeling and arrhythmogenesis. Mol Cell Biol. 2012. V. 32. P. 1056–1067. doi: 10.1128/MCB.06188-11.